Recent studies show that gastrointestinal hormones/growth factors may stimulate cell growth by stimulating multiple intracellular tyrosine phosphorylation (TyrP) signaling cascades as well as by transactivating growth factor receptors. However at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades. Our studies have been in two general areas, which include studies of intracellular signaling cascades primarily by tyrosine kinases and studies of tumoral growth attempting to develop novel agents for growth inhibition. Recent studies show that gastrointestinal hormones, similar to growth factors, may stimulate cell growth/cell signaling by stimulating multiple intracellular tyrosine phosphorylation (TyrP) cascades. Whereas these cascades have been extensively investigated with growth factors, little is known in this area with may gastrointestinal hormones. The goal of these studies is to clarify this area primarily concentrating on cholecystokinin receptor cascades and bombesin receptor activation using primarily pancreatic acini as a model natural cell system. Studies involving the ability of the Bn related peptide neuromedin B to stimulate growth of lung cancer cells were performed. These studies show that NMBR activation stiumulates transactivation of the EGF receptor which is dependent on activation of matrix metalloproteinases and the generation of reactive oxygen species. Studies of PKC theta activation are completed and will be submitted later this year. The ability of novel cytotoxic sulfur NSAID to alter growth of lung cancer cells was also studied this year. Furthermore,in collaboration with Prof A Giruad, the ability of glycine extended forms of GRP, which occur in large amounts in pregnant sheep, to stimulate cellular cascades, was studied.